Direct and indirect effects of leptin on adipocyte metabolism

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1842, Issue 3, 2014, Pages 414-423

  Harris, Ruth B S ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

Insulin; Leptin receptor; Lipogenesis; Lipolysis; Sympathetic nervous system

Indexed keywords

INSULIN; LEPTIN; LEPTIN RECEPTOR; TRIACYLGLYCEROL;

ADIPOCYTE; ADIPOSE TISSUE; ADRENERGIC SYSTEM; BODY FAT; BODY WEIGHT; CELL METABOLISM; CELL PROLIFERATION; FOOD INTAKE; GLUCOSE OXIDATION; HUMAN; HYDROLYSIS; INSULIN METABOLISM; INSULIN RELEASE; LIPID STORAGE; LIPOGENESIS; LIPOLYSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; SYMPATHETIC INNERVATION;

ANIMALIA; MUS;

INSULIN; LEPTIN RECEPTOR; LIPOGENESIS; LIPOLYSIS; SYMPATHETIC NERVOUS SYSTEM;

ADIPOCYTES; ADIPOSE TISSUE; ANIMALS; BODY FAT DISTRIBUTION; BODY WEIGHT; EATING; ENERGY METABOLISM; HUMANS; LEPTIN; MICE;

EID: 84893650900     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2013.05.009     Document Type: Review

References (191)

1. Adolph E.F. Urges to eat and drink in rats. Am. J. Physiol. 1947, 151:110-125.
2. Durnin J.V. 'Appetite' and the relationships between expenditure and intake of calories in man. J. Physiol. 1961, 156:294-306.
3. Fox F.W. The enigma of obesity. Lancet 1973, 2:1487-1488.
4. Taggart N. Diet, activity and body-weight. A study of variations in a woman. Br. J. Nutr. 1962, 16:223-235.
5. Mayer J. Glucostatic mechanism of regulation of food intake. N. Engl. J. Med. 1953, 249:13-16.
6. Mellinkoff S. Digestive system. Annu. Rev. Physiol. 1957, 19:175-204.
7. Brobeck J.R. Food intake as a mechanism of temperature regulation. Yale J. Biol. Med. 1948, 20:545-552.
8. Kennedy G.C. The role of depot fat in the hypothalamic control of food intake in rats. Proc. R. Soc. Lond. B Biol. Sci. 1953, 140:578-592.
9. Hervey G.R. The effects of lesions in the hypothalamus in parabiotic rats. J. Physiol. Lond. 1959, 145:336-352.
10. Coleman D.L. Effects of parabiosis of obese with diabetes and normal mice. Diabetologia 1973, 9:294-298.
11. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.
12. Bado A., Levasseur S., Attoub S., Kermorgant S., Laigneau J.P., Bortoluzzi M.N., Moizo L., Lehy T., Guerre-Millo M., Le Marchand-Brustel Y., Lewin M.J. The stomach is a source of leptin. Nature 1998, 394:790-793.
13. Vernooy J.H., Drummen N.E., van Suylen R.J., Cloots R.H., Moller G.M., Bracke K.R., Zuyderduyn S., Dentener M.A., Brusselle G.G., Hiemstra P.S., Wouters E.F. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax 2009, 64:26-32.
14. Hoggard N., Hunter L., Duncan J.S., Williams L.M., Trayhurn P., Mercer J.G. Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:11073-11078.
15. Wiesner G., Vaz M., Collier G., Seals D., Kaye D., Jennings G., Lambert G., Wilkinson D., Esler M. Leptin is released from the human brain: influence of adiposity and gender. J. Clin. Endocrinol. Metab. 1999, 84:2270-2274.
16. Mitchell S.E., Rees W.D., Hardie L.J., Hoggard N., Tadayyon M., Arch J.R., Trayhurn P. ob gene expression and secretion of leptin following differentiation of rat preadipocytes to adipocytes in primary culture. Biochem. Biophys. Res. Commun. 1997, 230:360-364.
17. Rousseau V., Becker D.J., Ongemba L.N., Rahier J., Henquin J.C., Brichard S.M. Developmental and nutritional changes of ob and PPAR gamma 2 gene expression in rat white adipose tissue. Biochem. J. 1997, 321:451-456.
18. Frederich R.C., Hamann A., Anderson S., Lollmann B., Lowell B.B., Flier J.S. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat. Med. 1995, 1:1311-1314.
19. Considine R.V., Sinha M.K., Heiman M.L., Kriauciunas A., Stephens T.W., Nyce M.R., Ohannesian J.P., Marco C.C., McKee L.J., Bauer T.L., Caro J.F. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 1996, 334:292-295.
20. Ogawa Y., Masuzaki H., Isse N., Okazaki T., Mori K., Shigemoto M., Satoh N., Tamura N., Hosoda K., Yoshimasa Y., et al. Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats. J. Clin. Invest. 1995, 96:1647-1652.
21. Harris R.B., Ramsay T.G., Smith S.R., Bruch R.C. Early and late stimulation of ob mRNA expression in meal-fed and overfed rats. J. Clin. Invest. 1996, 97:2020-2026.
22. Zhang Y., Guo K.Y., Diaz P.A., Heo M., Leibel R.L. Determinants of leptin gene expression in fat depots of lean mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2002, 282:R226-R234.
23. Barr V.A., Malide D., Zarnowski M.J., Taylor S.I., Cushman S.W. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology 1997, 138:4463-4472.
24. Roh C., Thoidis G., Farmer S.R., Kandror K.V. Identification and characterization of leptin-containing intracellular compartment in rat adipose cells. Am. J. Physiol. Endocrinol. Metab. 2000, 279:E893-E899.
25. Ye F., Than A., Zhao Y., Goh K.H., Chen P. Vesicular storage, vesicle trafficking, and secretion of leptin and resistin: the similarities, differences, and interplays. J. Endocrinol. 2010, 206:27-36.
26. Licinio J., Mantzoros C., Negrao A.B., Cizza G., Wong M.L., Bongiorno P.B., Chrousos G.P., Karp B., Allen C., Flier J.S., Gold P.W. Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat. Med. 1997, 3:575-579.
27. Sinha M.K., Sturis J., Ohannesian J., Magosin S., Stephens T., Heiman M.L., Polonsky K.S., Caro J.F. Ultradian oscillations of leptin secretion in humans. Biochem. Biophys. Res. Commun. 1996, 228:733-738.
28. Schoeller D.A., Cella L.K., Sinha M.K., Caro J.F. Entrainment of the diurnal rhythm of plasma leptin to meal timing. J. Clin. Invest. 1997, 100:1882-1887.
29. Thompson M.P. Meal-feeding specifically induces obese mRNA expression. Biochem. Biophys. Res. Commun. 1996, 224:332-337.
30. Havel P.J., Townsend R., Chaump L., Teff K. High-fat meals reduce 24-h circulating leptin concentrations in women. Diabetes 1999, 48:334-341.
31. Boden G., Chen X., Mozzoli M., Ryan I. Effect of fasting on serum leptin in normal human subjects. J. Clin. Endocrinol. Metab. 1996, 81:3419-3423.
32. Ricci M.R., Fried S.K., Mittleman K.D. Acute cold exposure decreases plasma leptin in women. Metabolism 2000, 49:421-423.
33. Mueller W.M., Gregoire F.M., Stanhope K.L., Mobbs C.V., Mizuno T.M., Warden C.H., Stern J.S., Havel P.J. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology 1998, 139:551-558.
34. Cammisotto P.G., Gelinas Y., Deshaies Y., Bukowiecki L.J. Regulation of leptin secretion from white adipocytes by insulin, glycolytic substrates, and amino acids. Am. J. Physiol. Endocrinol. Metab. 2005, 289:E166-E171.
35. Gettys T.W., Harkness P.J., Watson P.M. The beta 3-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes. Endocrinology 1996, 137:4054-4057.
36. Slieker L.J., Sloop K.W., Surface P.L., Kriauciunas A., LaQuier F., Manetta J., Bue-Valleskey J., Stephens T.W. Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J. Biol. Chem. 1996, 271:5301-5304.
37. Rentsch J., Chiesi M. Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Lett. 1996, 379:55-59.
38. Shintani M., Nishimura H., Yonemitsu S., Masuzaki H., Ogawa Y., Hosoda K., Inoue G., Yoshimasa Y., Nakao K. Downregulation of leptin by free fatty acids in rat adipocytes: effects of triacsin C, palmitate, and 2-bromopalmitate. Metabolism 2000, 49:326-330.
39. Szkudelski T. Intracellular mediators in regulation of leptin secretion from adipocytes. Physiol. Res. 2007, 56:503-512.
40. Lee M.J., Fried S.K. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E1230-E1238.
41. Lee G.H., Proenca R., Montez J.M., Carroll K.M., Darvishzadeh J.G., Lee J.I., Friedman J.M. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996, 379:632-635.
42. Baumann H., Morella K.K., White D.W., Dembski M., Bailon P.S., Kim H., Lai C.F., Tartaglia L.A. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:8374-8378.
43. Ghilardi N., Ziegler S., Wiestner A., Stoffel R., Heim M.H., Skoda R.C. Defective STAT signaling by the leptin receptor in diabetic mice. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:6231-6235.
44. Kim Y.B., Uotani S., Pierroz D.D., Flier J.S., Kahn B.B. In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinology 2000, 141:2328-2339.
45. Niswender K.D., Morton G.J., Stearns W.H., Rhodes C.J., Myers M.G., Schwartz M.W. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001, 413:794-795.
46. Banks A.S., Davis S.M., Bates S.H., Myers M.G. Activation of downstream signals by the long form of the leptin receptor. J. Biol. Chem. 2000, 275:14563-14572.
47. Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., Schwartz M.W., Myers M.G. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003, 421:856-859.
48. Kastin A.J., Pan W., Maness L.M., Koletsky R.J., Ernsberger P. Decreased transport of leptin across the blood-brain barrier in rats lacking the short form of the leptin receptor. Peptides 1999, 20:1449-1453.
49. Uotani S., Bjorbaek C., Tornoe J., Flier J.S. Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation. Diabetes 1999, 48:279-286.
50. Schaab M., Kausch H., Klammt J., Nowicki M., Anderegg U., Gebhardt R., Rose-John S., Scheller J., Thiery J., Kratzsch J. Novel regulatory mechanisms for generation of the soluble leptin receptor: implications for leptin action. PLoS One 2012, 7:e34787.
51. Ge H., Huang L., Pourbahrami T., Li C. Generation of soluble leptin receptor by ectodomain shedding of membrane-spanning receptors in vitro and in vivo. J. Biol. Chem. 2002, 277:45898-45903.
52. Liu C., Liu X.J., Barry G., Ling N., Maki R.A., De Souza E.B. Expression and characterization of a putative high affinity human soluble leptin receptor. Endocrinology 1997, 138:3548-3554.
53. Yang G., Ge H., Boucher A., Yu X., Li C. Modulation of direct leptin signaling by soluble leptin receptor. Mol. Endocrinol. 2004, 18:1354-1362.
54. Zastrow O., Seidel B., Kiess W., Thiery J., Keller E., Bottner A., Kratzsch J. The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int. J. Obes. Relat. Metab. Disord. 2003, 27:1472-1478.
55. Sinha M.K., Caro J.F. Clinical aspects of leptin. Vitam. Horm. 1998, 54:1-30.
56. Brabant G., Nave H., Mayr B., Behrend M., van Harmelen V., Arner P. Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women. J. Clin. Endocrinol. Metab. 2002, 87:3966-3970.
57. Scott M.M., Lachey J.L., Sternson S.M., Lee C.E., Elias C.F., Friedman J.M., Elmquist J.K. Leptin targets in the mouse brain. J. Comp. Neurol. 2009, 514:518-532.
58. Hoggard N., Mercer J.G., Rayner D.V., Moar K., Trayhurn P., Williams L.M. Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem. Biophys. Res. Commun. 1997, 232:383-387.
59. Zamorano P.L., Mahesh V.B., De Sevilla L.M., Chorich L.P., Bhat G.K., Brann D.W. Expression and localization of the leptin receptor in endocrine and neuroendocrine tissues of the rat. Neuroendocrinology 1997, 65:223-228.
60. Kielar D., Clark J.S., Ciechanowicz A., Kurzawski G., Sulikowski T., Naruszewicz M. Leptin receptor isoforms expressed in human adipose tissue. Metabolism 1998, 47:844-847.
61. Ramsay T.G., Richards M.P. Hormonal regulation of leptin and leptin receptor expression in porcine subcutaneous adipose tissue. J. Anim. Sci. 2004, 82:3486-3492.
62. Aprath-Husmann I., Rohrig K., Gottschling-Zeller H., Skurk T., Scriba D., Birgel M., Hauner H. Effects of leptin on the differentiation and metabolism of human adipocytes. Int. J. Obes. Relat. Metab. Disord. 2001, 25:1465-1470.
63. Lollmann B., Gruninger S., Stricker-Krongrad A., Chiesi M. Detection and quantification of the leptin receptor splice variants Ob-Ra, b, and, e in different mouse tissues. Biochem. Biophys. Res. Commun. 1997, 238:648-652.
64. Bornstein S.R., Abu-Asab M., Glasow A., Path G., Hauner H., Tsokos M., Chrousos G.P., Scherbaum W.A. Immunohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture. Diabetes 2000, 49:532-538.
65. Obradovic T., Meadows G.G. Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice. Alcohol. Clin. Exp. Res. 2002, 26:255-262.
66. Huan J.N., Li J., Han Y., Chen K., Wu N., Zhao A.Z. Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance. J. Biol. Chem. 2003, 278:45638-45650.
67. Bamshad M., Aoki V.T., Adkison M.G., Warren W.S., Bartness T.J. Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am. J. Physiol. 1998, 275:R291-R299.
68. Lord G.M., Matarese G., Howard J.K., Baker R.J., Bloom S.R., Lechler R.I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998, 394:897-901.
69. Agrawal S., Gollapudi S., Su H., Gupta S. Leptin activates human B cells to secrete TNF-alpha, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J. Clin. Immunol. 2011, 31:472-478.
70. Santos-Alvarez J., Goberna R., Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell. Immunol. 1999, 194:6-11.
71. Paz-Filho G., Mastronardi C., Franco C.B., Wang K.B., Wong M.L., Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq. Bras. Endocrinol. Metabol. 2012, 56:597-607.
72. Carlton E.D., Demas G.E., French S.S. Leptin, a neuroendocrine mediator of immune responses, inflammation, and sickness behaviors. Horm. Behav. 2012, 62:272-279.
73. Faggioni R., Jones-Carson J., Reed D.A., Dinarello C.A., Feingold K.R., Grunfeld C., Fantuzzi G. Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:2367-2372.
74. Shen J., Sakaida I., Uchida K., Terai S., Okita K. Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci. 2005, 77:1502-1515.
75. Sun S., Ji Y., Kersten S., Qi L. Mechanisms of inflammatory responses in obese adipose tissue. Annu. Rev. Nutr. 2012, 32:261-286.
76. Hotamisligil G.S., Murray D.L., Choy L.N., Spiegelman B.M. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc. Natl. Acad. Sci. U. S. A. 1994, 91:4854-4858.
77. Bullo M., Garcia-Lorda P., Megias I., Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes. Res. 2003, 11:525-531.
78. Pelleymounter M.A., Cullen M.J., Healy D., Hecht R., Winters D., McCaleb M. Efficacy of exogenous recombinant murine leptin in lean and obese 10- to 12-mo-old female CD-1 mice. Am. J. Physiol. 1998, 275:R950-R959.
79. Halaas J.L., Gajiwala K.S., Maffei M., Cohen S.L., Chait B.T., Rabinowitz D., Lallone R.L., Burley S.K., Friedman J.M. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995, 269:543-546.
80. Campfield L.A., Smith F.J., Guisez Y., Devos R., Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995, 269:546-549.
81. El-Haschimi K., Pierroz D.D., Hileman S.M., Bjorbaek C., Flier J.S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J. Clin. Invest. 2000, 105:1827-1832.
82. Halaas J.L., Boozer C., Blair-West J., Fidahusein N., Denton D.A., Friedman J.M. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:8878-8883.
83. Munzberg H., Flier J.S., Bjorbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 2004, 145:4880-4889.
84. Enriori P.J., Sinnayah P., Simonds S.E., Garcia Rudaz C., Cowley M.A. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J. Neurosci. 2011, 31:12189-12197.
85. Wang Z., Zhou Y.T., Kakuma T., Lee Y., Kalra S.P., Kalra P.S., Pan W., Unger R.H. Leptin resistance of adipocytes in obesity: role of suppressors of cytokine signaling. Biochem. Biophys. Res. Commun. 2000, 277:20-26.
86. Wang M.Y., Orci L., Ravazzola M., Unger R.H. Fat storage in adipocytes requires inactivation of leptin's paracrine activity: implications for treatment of human obesity. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:18011-18016.
87. Bjorbaek C., Elmquist J.K., Frantz J.D., Shoelson S.E., Flier J.S. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol. Cell 1998, 1:619-625.
88. Seron K., Corset L., Vasseur F., Boutin P., Gomez-Ambrosi J., Salvador J., Fruhbeck G., Froguel P. Distinct impaired regulation of SOCS3 and long and short isoforms of the leptin receptor in visceral and subcutaneous fat of lean and obese women. Biochem. Biophys. Res. Commun. 2006, 348:1232-1238.
89. Muller G., Ertl J., Gerl M., Preibisch G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J. Biol. Chem. 1997, 272:10585-10593.
90. Fruhbeck G., Aguado M., Martinez J.A. In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem. Biophys. Res. Commun. 1997, 240:590-594.
91. Banks W.A., DiPalma C.R., Farrell C.L. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 1999, 20:1341-1345.
92. Dyer C.J., Simmons J.M., Matteri R.L., Keisler D.H. Leptin receptor mRNA is expressed in ewe anterior pituitary and adipose tissues and is differentially expressed in hypothalamic regions of well-fed and feed-restricted ewes. Domest. Anim. Endocrinol. 1997, 14:119-128.
93. MacDougald O.A., Hwang C.S., Fan H., Lane M.D. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc. Natl. Acad. Sci. U. S. A. 1995, 92:9034-9037.
94. Harris R.B., Zhou J., Redmann S.M., Smagin G.N., Smith S.R., Rodgers E., Zachwieja J.J. A leptin dose-response study in obese (ob/ob) and lean (+/?) mice. Endocrinology 1998, 139:8-19.
95. Minokoshi Y., Haque M.S., Shimazu T. Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes 1999, 48:287-291.
96. Kamohara S., Burcelin R., Halaas J.L., Friedman J.M., Charron M.J. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 1997, 389:374-377.
97. Zierath J.R., Frevert E.U., Ryder J.W., Berggren P.O., Kahn B.B. Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes. Diabetes 1998, 47:1-4.
98. Perez C., Fernandez-Galaz C., Fernandez-Agullo T., Arribas C., Andres A., Ros M., Carrascosa J.M. Leptin impairs insulin signaling in rat adipocytes. Diabetes 2004, 53:347-353.
99. Tracey A.S., Gresser M.J. Interaction of vanadate with phenol and tyrosine: implications for the effects of vanadate on systems regulated by tyrosine phosphorylation. Proc. Natl. Acad. Sci. U. S. A. 1986, 83:609-613.
100. Walder K., Filippis A., Clark S., Zimmet P., Collier G.R. Leptin inhibits insulin binding in isolated rat adipocytes. J. Endocrinol. 1997, 155:R5-R7.
101. Senn J.J., Klover P.J., Nowak I.A., Zimmers T.A., Koniaris L.G., Furlanetto R.W., Mooney R.A. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J. Biol. Chem. 2003, 278:13740-13746.
102. Bjorbaek C., El-Haschimi K., Frantz J.D., Flier J.S. The role of SOCS-3 in leptin signaling and leptin resistance. J. Biol. Chem. 1999, 274:30059-30065.
103. Wang M.Y., Lee Y., Unger R.H. Novel form of lipolysis induced by leptin. J. Biol. Chem. 1999, 274:17541-17544.
104. Bai Y., Zhang S., Kim K.S., Lee J.K., Kim K.H. Obese gene expression alters the ability of 30A5 preadipocytes to respond to lipogenic hormones. J. Biol. Chem. 1996, 271:13939-13942.
105. Ceddia R.B., William W.N., Lima F.B., Flandin P., Curi R., Giacobino J.P. Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes. Eur. J. Biochem. 2000, 267:5952-5958.
106. Ceddia R.B., William W.N., Lima F.B., Curi R. Leptin inhibits insulin-stimulated incorporation of glucose into lipids and stimulates glucose decarboxylation in isolated rat adipocytes. J. Endocrinol. 1998, 158:R7-R9.
107. Gulick T., Cresci S., Caira T., Moore D.D., Kelly D.P. The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc. Natl. Acad. Sci. U. S. A. 1994, 91:11012-11016.
108. Kakuma T., Wang Z.W., Pan W., Unger R.H., Zhou Y.T. Role of leptin in peroxisome proliferator-activated receptor gamma coactivator-1 expression. Endocrinology 2000, 141:4576-4582.
109. Vega R.B., Huss J.M., Kelly D.P. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol. Cell. Biol. 2000, 20:1868-1876.
110. William W.N., Ceddia R.B., Curi R. Leptin controls the fate of fatty acids in isolated rat white adipocytes. J. Endocrinol. 2002, 175:735-744.
111. Jaubert A.M., Penot G., Niang F., Durant S., Forest C. Rapid nitration of adipocyte phosphoenolpyruvate carboxykinase by leptin reduces glyceroneogenesis and induces fatty acid release. PLoS One 2012, 7:e40650.
112. Rodriguez V.M., Macarulla M.T., Echevarria E., Portillo M.P. Lipolysis induced by leptin in rat adipose tissue from different anatomical locations. Eur. J. Nutr. 2003, 42:149-153.
113. Siegrist-Kaiser C.A., Pauli V., Juge-Aubry C.E., Boss O., Pernin A., Chin W.W., Cusin I., Rohner-Jeanrenaud F., Burger A.G., Zapf J., Meier C.A. Direct effects of leptin on brown and white adipose tissue. J. Clin. Invest. 1997, 100:2858-2864.
114. Newby D., Gertler A., Vernon R.G. Effects of recombinant ovine leptin on in vitro lipolysis and lipogenesis in subcutaneous adipose tissue from lactating and nonlactating sheep. J. Anim. Sci. 2001, 79:445-452.
115. Elimam A., Kamel A., Marcus C. In vitro effects of leptin on human adipocyte metabolism. Horm. Res. 2002, 58:88-93.
116. Ramsay T.G. Porcine leptin alters insulin inhibition of lipolysis in porcine adipocytes in vitro. J. Anim. Sci. 2001, 79:653-657.
117. Kim W.K., Lee C.Y., Kang M.S., Kim M.H., Ryu Y.H., Bae K.H., Shin S.J., Lee S.C., Ko Y. Effects of leptin on lipid metabolism and gene expression of differentiation-associated growth factors and transcription factors during differentiation and maturation of 3T3-L1 preadipocytes. Endocr. J. 2008, 55:827-837.
118. Li Y.C., Zheng X.L., Liu B.T., Yang G.S. Regulation of ATGL expression mediated by leptin in vitro in porcine adipocyte lipolysis. Mol. Cell. Biochem. 2010, 333:121-128.
119. Lee G., Li C., Montez J., Halaas J., Darvishzadeh J., Friedman J.M. Leptin receptor mutations in 129 db3J/db3J mice and NIH facp/facp rats. Mamm. Genome 1997, 8:445-447.
120. Guo K., McMinn J.E., Ludwig T., Yu Y.H., Yang G., Chen L., Loh D., Li C., Chua S., Zhang Y. Disruption of peripheral leptin signaling in mice results in hyperleptinemia without associated metabolic abnormalities. Endocrinology 2007, 148:3987-3997.
121. Kowalski T.J., Liu S.M., Leibel R.L., Chua S.C. Transgenic complementation of leptin-receptor deficiency. I. Rescue of the obesity/diabetes phenotype of LEPR-null mice expressing a LEPR-B transgene. Diabetes 2001, 50:425-435.
122. Cohen P., Zhao C., Cai X., Montez J.M., Rohani S.C., Feinstein P., Mombaerts P., Friedman J.M. Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest. 2001, 108:1113-1121.
123. McMinn J.E., Liu S.M., Liu H., Dragatsis I., Dietrich P., Ludwig T., Boozer C.N., Chua S.C. Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility. Am. J. Physiol. Endocrinol. Metab. 2005, 289:E403-E411.
124. Chen H., Charlat O., Tartaglia L.A., Woolf E.A., Weng X., Ellis S.J., Lakey N.D., Culpepper J., Moore K.J., Breitbart R.E., Duyk G.M., Tepper R.I., Morgenstern J.P. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996, 84:491-495.
125. Bowers R.R., Festuccia W.T., Song C.K., Shi H., Migliorini R.H., Bartness T.J. Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 286:R1167-R1175.
126. Rooks C.R., Penn D.M., Kelso E., Bowers R.R., Bartness T.J., Harris R.B. Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2005, 289:R92-R102.
127. Harris R.B. Sympathetic denervation of one white fat depot changes norepinephrine content and turnover in intact white and brown fat depots. Obesity (Silver Spring) 2012, 20:1355-1364.
128. Bates S.H., Gardiner J.V., Jones R.B., Bloom S.R., Bailey C.J. Acute stimulation of glucose uptake by leptin in l6 muscle cells. Horm. Metab. Res. 2002, 34:111-115.
129. Ashwell M. The use of the adipose tissue transplantation technique to demonstrate that abnormalities in the adipose tissue metabolism of genetically obese mice are due to extrinsic rather than intrinsic factors. Int. J. Obes. 1985, 9(Suppl. 1):77-82.
130. Enser M., Ashwell M. Fatty acid composition of triglycerides from adipose tissue transplanted between obese and lean mice. Lipids 1983, 18:776-780.
131. Guo K., Mogen J., Struzzi S., Zhang Y. Preadipocyte transplantation: an in vivo study of direct leptin signaling on adipocyte morphogenesis and cell size. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009, 296:R1339-R1347.
132. Kolaczynski J.W., Nyce M.R., Considine R.V., Boden G., Nolan J.J., Henry R., Mudaliar S.R., Olefsky J., Caro J.F. Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes 1996, 45:699-701.
133. Shimomura I., Hammer R.E., Ikemoto S., Brown M.S., Goldstein J.L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999, 401:73-76.
134. Emilsson V., Liu Y.L., Cawthorne M.A., Morton N.M., Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes 1997, 46:313-316.
135. Kieffer T.J., Heller R.S., Habener J.F. Leptin receptors expressed on pancreatic beta-cells. Biochem. Biophys. Res. Commun. 1996, 224:522-527.
136. Kulkarni R.N., Wang Z.L., Wang R.M., Hurley J.D., Smith D.M., Ghatei M.A., Withers D.J., Gardiner J.V., Bailey C.J., Bloom S.R. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J. Clin. Invest. 1997, 100:2729-2736.
137. Poitout V., Rouault C., Guerre-Millo M., Briaud I., Reach G. Inhibition of insulin secretion by leptin in normal rodent islets of Langerhans. Endocrinology 1998, 139:822-826.
138. Kieffer T.J., Heller R.S., Leech C.A., Holz G.G., Habener J.F. Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 1997, 46:1087-1093.
139. Lam N.T., Cheung A.T., Riedel M.J., Light P.E., Cheeseman C.I., Kieffer T.J. Leptin reduces glucose transport and cellular ATP levels in INS-1 beta-cells. J. Mol. Endocrinol. 2004, 32:415-424.
140. Seufert J., Kieffer T.J., Habener J.F. Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:674-679.
141. Zhou Y.T., Shimabukuro M., Koyama K., Lee Y., Wang M.Y., Trieu F., Newgard C.B., Unger R.H. Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:6386-6390.
142. Shimabukuro M., Koyama K., Chen G., Wang M.Y., Trieu F., Lee Y., Newgard C.B., Unger R.H. Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:4637-4641.
143. Cases J.A., Gabriely I., Ma X.H., Yang X.M., Michaeli T., Fleischer N., Rossetti L., Barzilai N. Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo. Diabetes 2001, 50:348-352.
144. Gray S.L., Donald C., Jetha A., Covey S.D., Kieffer T.J. Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptin signaling. Endocrinology 2010, 151:4178-4186.
145. Pelleymounter M.A., Cullen M.J., Baker M.B., Hecht R., Winters D., Boone T., Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995, 269:540-543.
146. Barzilai N., Wang J., Massilon D., Vuguin P., Hawkins M., Rossetti L. Leptin selectively decreases visceral adiposity and enhances insulin action. J. Clin. Invest. 1997, 100:3105-3110.
147. Berglund E.D., Vianna C.R., Donato J., Kim M.H., Chuang J.C., Lee C.E., Lauzon D.A., Lin P., Brule L.J., Scott M.M., Coppari R., Elmquist J.K. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J. Clin. Invest. 2012, 122:1000-1009.
148. Reitman M.L., Gavrilova O. A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes. Int. J. Obes. Relat. Metab. Disord. 2000, 24(Suppl. 4):S11-S14.
149. Ebihara K., Ogawa Y., Masuzaki H., Shintani M., Miyanaga F., Aizawa-Abe M., Hayashi T., Hosoda K., Inoue G., Yoshimasa Y., Gavrilova O., Reitman M.L., Nakao K. Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes 2001, 50:1440-1448.
150. Gavrilova O., Marcus-Samuels B., Graham D., Kim J.K., Shulman G.I., Castle A.L., Vinson C., Eckhaus M., Reitman M.L. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J. Clin. Invest. 2000, 105:271-278.
151. Colombo C., Cutson J.J., Yamauchi T., Vinson C., Kadowaki T., Gavrilova O., Reitman M.L. Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy. Diabetes 2002, 51:2727-2733.
152. Asilmaz E., Cohen P., Miyazaki M., Dobrzyn P., Ueki K., Fayzikhodjaeva G., Soukas A.A., Kahn C.R., Ntambi J.M., Socci N.D., Friedman J.M. Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. J. Clin. Invest. 2004, 113:414-424.
153. Moran S.A., Patten N., Young J.R., Cochran E., Sebring N., Reynolds J., Premkumar A., Depaoli A.M., Skarulis M.C., Oral E.A., Gorden P. Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism 2004, 53:513-519.
154. Javor E.D., Cochran E.K., Musso C., Young J.R., Depaoli A.M., Gorden P. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes 2005, 54:1994-2002.
155. Ebihara K., Kusakabe T., Hirata M., Masuzaki H., Miyanaga F., Kobayashi N., Tanaka T., Chusho H., Miyazawa T., Hayashi T., Hosoda K., Ogawa Y., DePaoli A.M., Fukushima M., Nakao K. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J. Clin. Endocrinol. Metab. 2007, 92:532-541.
156. Kamran F., Rother K.I., Cochran E., Safar Zadeh E., Gorden P., Brown R.J. Consequences of stopping and restarting leptin in an adolescent with lipodystrophy. Horm. Res. Paediatr. 2012, 78:320-325.
157. Petersen K.F., Oral E.A., Dufour S., Befroy D., Ariyan C., Yu C., Cline G.W., DePaoli A.M., Taylor S.I., Gorden P., Shulman G.I. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J. Clin. Invest. 2002, 109:1345-1350.
158. Chen G., Koyama K., Yuan X., Lee Y., Zhou Y.T., O.D.R, Newgard C.B., Unger R.H. Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:14795-14799.
159. Chinookoswong N., Wang J.L., Shi Z.Q. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes 1999, 48:1487-1492.
160. Hidaka S., Yoshimatsu H., Kondou S., Tsuruta Y., Oka K., Noguchi H., Okamoto K., Sakino H., Teshima Y., Okeda T., Sakata T. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J. 2002, 16:509-518.
161. Lin C.Y., Higginbotham D.A., Judd R.L., White B.D. Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am. J. Physiol. Endocrinol. Metab. 2002, 282:E1084-E1091.
162. Denroche H.C., Levi J., Wideman R.D., Sequeira R.M., Huynh F.K., Covey S.D., Kieffer T.J. Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes 2011, 60:1414-1423.
163. Wang J., Wernette C.M., Judd R.L., Huggins K.W., White B.D. Guanethidine treatment does not block the ability of central leptin administration to decrease blood glucose concentrations in streptozotocin-induced diabetic rats. J. Endocrinol. 2008, 198:541-548.
164. Yu X., Park B.H., Wang M.Y., Wang Z.V., Unger R.H. Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:14070-14075.
165. Lee Y., Wang M.Y., Du X.Q., Charron M.J., Unger R.H. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 2011, 60:391-397.
166. Tuduri E., Marroqui L., Soriano S., Ropero A.B., Batista T.M., Piquer S., Lopez-Boado M.A., Carneiro E.M., Gomis R., Nadal A., Quesada I. Inhibitory effects of leptin on pancreatic alpha-cell function. Diabetes 2009, 58:1616-1624.
167. Youngstrom T.G., Bartness T.J. Catecholaminergic innervation of white adipose tissue in Siberian hamsters. Am. J. Physiol. 1995, 268:R744-R751.
168. Carpene C., Bousquet-Melou A., Galitzky J., Berlan M., Lafontan M. Lipolytic effects of beta 1-, beta 2-, and beta 3-adrenergic agonists in white adipose tissue of mammals. Ann. N. Y. Acad. Sci. 1998, 839:186-189.
169. Dunbar J.C., Hu Y., Lu H. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 1997, 46:2040-2043.
170. Scarpace P.J., Matheny M. Leptin induction of UCP1 gene expression is dependent on sympathetic innervation. Am. J. Physiol. 1998, 275:E259-E264.
171. Young C.N., Morgan D.A., Butler S.D., Mark A.L., Davisson R.L. The brain subfornical organ mediates leptin-induced increases in renal sympathetic activity but not its metabolic effects. Hypertension 2013, 61:737-744.
172. da Silva A.A., Kuo J.J., Hall J.E. Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin. Hypertension 2004, 43:1312-1317.
173. Haynes W.G., Morgan D.A., Djalali A., Sivitz W.I., Mark A.L. Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension 1999, 33:542-547.
174. Song C.K., Vaughan C.H., Keen-Rhinehart E., Harris R.B., Richard D., Bartness T.J. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008, 295:R417-R428.
175. Sahu A. Resistance to the satiety action of leptin following chronic central leptin infusion is associated with the development of leptin resistance in neuropeptide Y neurones. J. Neuroendocrinol. 2002, 14:796-804.
176. Penn D.M., Jordan L.C., Kelso E.W., Davenport J.E., Harris R.B. Effects of central or peripheral leptin administration on norepinephrine turnover in defined fat depots. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 291:R1613-R1621.
177. Wang Z.W., Zhou Y.T., Lee Y., Higa M., Kalra S.P., Unger R.H. Hyperleptinemia depletes fat from denervated fat tissue. Biochem. Biophys. Res. Commun. 1999, 260:653-657.
178. Buettner C., Muse E.D., Cheng A., Chen L., Scherer T., Pocai A., Su K., Cheng B., Li X., Harvey-White J., Schwartz G.J., Kunos G., Rossetti L. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 2008, 14:667-675.
179. Kim J.B., Spiegelman B.M. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 1996, 10:1096-1107.
180. Tontonoz P., Hu E., Spiegelman B.M. Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor gamma. Curr. Opin. Genet. Dev. 1995, 5:571-576.
181. Tanti J.F., Ceppo F., Jager J., Berthou F. Implication of inflammatory signaling pathways in obesity-induced insulin resistance. Front. Endocrinol. (Lausanne) 2012, 3:181.
182. Shen J., Tanida M., Niijima A., Nagai K. In vivo effects of leptin on autonomic nerve activity and lipolysis in rats. Neurosci. Lett. 2007, 416:193-197.
183. Bartness T.J., Song C.K., Demas G.E. SCN efferents to peripheral tissues: implications for biological rhythms. J. Biol. Rhythms 2001, 16:196-204.
184. Elmquist J.K., Bjorbaek C., Ahima R.S., Flier J.S., Saper C.B. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 1998, 395:535-547.
185. Ramsay T.G. Porcine preadipocyte proliferation and differentiation: a role for leptin?. J. Anim. Sci. 2005, 83:2066-2074.
186. Machinal-Quelin F., Dieudonne M.N., Leneveu M.C., Pecquery R., Giudicelli Y. Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways. Am. J. Physiol. Cell Physiol. 2002, 282:C853-C863.
187. Wagoner B., Hausman D.B., Harris R.B. Direct and indirect effects of leptin on preadipocyte proliferation and differentiation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 290:R1557-R1564.
188. Bogacka I., Roane D.S., Xi X., Zhou J., Li B., Ryan D.H., Martin R.J. Expression levels of genes likely involved in glucose-sensing in the obese Zucker rat brain. Nutr. Neurosci. 2004, 7:67-74.
189. Rosen E.D., Sarraf P., Troy A.E., Bradwin G., Moore K., Milstone D.S., Spiegelman B.M., Mortensen R.M. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 1999, 4:611-617.
190. Green H., Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975, 5:19-27.
191. Zhou Y.T., Wang Z.W., Higa M., Newgard C.B., Unger R.H. Reversing adipocyte differentiation: implications for treatment of obesity. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:2391-2395.